Includes bibliographical references.

Hospitalization and Combined Use of Opioids, Benzodiazepines, and Muscle Relaxants in the United States -- Cost-effective Analysis of Proton Pump Inhibitors in Long-term Management of Gastroesophageal Reflux Disease: A Narrative Review -- Evaluating Pharmacy Practice in Hospital Settings in Jeddah City, Saudi Arabia: Prescribing and Transcribing—2018 -- Formulation and Stability Study of Omeprazole Oral Liquid Suspension for Pediatric Patients -- Comparison of 3 Surveillance Methods to Detect Potential Controlled Substance Diversion in an Academic Medical Center -- Compatibility of Y-Site Injection of Meropenem Trihydrate With 101 Other Injectable Drugs -- A Case of Antibiotic-Induced Posterior Reversible Encephalopathy Syndrome.

[Article Title: Hospitalization and Combined Use of Opioids, Benzodiazepines, and Muscle Relaxants in the United States / Jonathan H. Watanabe and Jincheng Yang, p. 286-291]

Abstract:

Introduction: Concurrent opioid and benzodiazepine use (“double-threat”) and double-threat and muscle relaxant use (“triple-threat”) are postulated to increase morbidity versus opioids alone. Study objectives were to measure association between double- and triple-threat exposure and hospitalizations in a validated, nationally representative database of the United States.

Methods: A retrospective cohort study was conducted using the 2013 and 2014 Medical Expenditure Panel Survey (MEPS) longitudinal dataset and affiliated Prescribed Medicines Files. Association between 2013 and 2014 double- and triple-threat exposures and outcome of hospitalizations compared to nonusers, opioid users, and all combinations were assessed via logistic regression. The cohort surveyed in MEPS has been weighted to be reflective of the actual US population in the years 2013 and 2014. Logistic regression applying the subject-level MEPS survey weights was performed to measure association via odds ratios (ORs) of medication exposures with the outcome of all-cause hospitalization. Study subjects were categorized into exposure groups as nonusers (nonuse of opioids, benzodiazepines, or muscle relaxants), opioid users, benzodiazepine users, muscle relaxant users, “double-threat” users, and “triple-threat” users. Analyses were conducted using RStudio® 1.1.5 (Boston, MA) with α level = 0.05 for all comparisons.

Results: Opioids, benzodiazepines, and muscle relaxants were used in 11.9% (38.4 million), 4.2% (13.5 million), and 3.4% (10.9 million) lives of the United States in 2013, respectively. Double-threat prevalence rose from 1.6% to 1.9% from 2013 to 2014. Triple-threat prevalence remained unchanged at 0.53%. Compared to nonusers, triple-threat patients increased hospitalization probability with ORs of 8.52 (95% confidence interval [CI]: 8.50-8.55) in 2013, 5.06 (95% CI: 5.04-5.08) in 2014, and 4.61 (95% CI: 4.59-4.63) in the 2013-2014 longitudinal analysis. Compared to nonusers, double-threat patients increased hospitalization probability with ORs of 5.71 (95% CI: 5.69-5.72) in 2013, 11.47 (95% CI: 11.44-11.49) in 2014, and 5.59 (95% CI: 5.57-5.60) in the longitudinal analysis.

Conclusion: Concurrent opioid and benzodiazepine use and opioid, benzodiazepine, and muscle relaxant use were associated with increased hospitalization likelihood. Amplified efforts in surveillance, prescribing, monitoring, and deprescribing for concurrent opioid, benzodiazepine, and muscle relaxant use are needed to reduce this public health concern.

https://doi.org/10.1177/0018578719894702

[Article Title: Cost-effective Analysis of Proton Pump Inhibitors in Long-term Management of Gastroesophageal Reflux Disease: A Narrative Review / Shazia Jamshed, Akshaya Srikanth Bhagavathula, Sheikh Muhammad Zeeshan Qadar, Umaira Alauddin, Sana Shamim and Sohail Hasan, p. 292-305]

Abstract:

Background: Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder that results from regurgitation of acid from the stomach into the esophagus. Treatment available for GERD includes lifestyle changes, antacids, histamine-2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), and anti-reflux surgery.

Aim: The aim of this review is to assess the cost-effectiveness of the use of PPIs in the long-term management of patients with GERD.

Method: We searched in PubMed to identify related original articles with close consideration based on inclusion and exclusion criteria to choose the best studies for this narrative review. The first section compares the cost-effectiveness of PPIs with H2RAs in long-term heartburn management. The other sections shall only discuss the cost-effectiveness of PPIs in 5 different strategies, namely, continuous (step-up, step-down, and maintenance), on-demand, and intermittent therapies.

Results: Of 55 articles published, 10 studies published from 2000 to 2015 were included. Overall, PPIs are more effective in relieving heartburn in comparison with ranitidine. The use of PPIs in managing heartburn in long-term consumption of nonsteroidal anti-inflammatory drug (NSAID) has higher cost compared with H2RA. However, if the decision-maker is willing to pay more than US$174 788.60 per extra quality-adjusted life year (QALY), then the optimal strategy is traditional NSAID (tNSAID) and PPIs. The probability of being cost-effective was also highest for NSAID and PPI co-therapy users. On-demand PPI treatment strategy showed dominant with an incremental cost-effectiveness ratio of US$2197 per QALY gained and was most effective and cost saving compared with all the other treatments. The average cost-effectiveness ratio was lower for rabeprazole therapy than for ranitidine therapy.

Conclusion: Our review revealed that long-term treatment with PPIs is effective but costly. To achieve long-term cost-effective approach, we recommend on-demand approach to treat heartburn symptoms, but if the symptoms persist, treatment with continuous step-down therapy should be applied.

https://doi.org/10.1177/0018578719893378

[Article Title: Evaluating Pharmacy Practice in Hospital Settings in Jeddah City, Saudi Arabia: Prescribing and Transcribing—2018 / Ahmed Essam Altyar, Samaher Abdullah Sadoun, Rahaf Saad Alradadi and Sarah Sultan Aljohani, p. 306-313]

Abstract:

Purpose: The aim of this study was to evaluate the prescription and transcription processes in hospital settings in Jeddah city, Saudi Arabia.

Method: A customized version of the original American Society of Health-System Pharmacists (ASHP) survey was distributed to a total of 26 hospitals in Jeddah city that fits our criteria starting from December 2017. Hospitals’ names were adopted from the Ministry of Health and Jeddah Municipality websites. All questionnaires were collected in June 2018. After that, they were classified according to the type of care provided by the hospital, size, ownership, teaching affiliation, and accreditation. Data were entered electronically using Google forms, and then Microsoft Excel was used to conduct descriptive statistics.

Results: The survey had a response rate of 57%. A strict formulary system was adopted in 53.3% of hospitals, and clinical practice guidelines were used to optimize medication use in 86.7% of hospitals. Pharmacists do not have the authority to write medication orders in about 86.7% of hospitals and only 40.0% of hospitals have pharmacists routinely assigned to patient care units. However, Pharmacists actively provided consultation, mostly in drug information (80.0%). Computerized prescriber order entry (CPOE) is used to receive medication orders electronically in 80.0% of hospitals, and electronic health record (EHR) is used in about 53.3% of hospitals and 50.0% of those hospitals have pharmacists who document their clinical intervention in EHR.

Conclusion: Survey results suggest that pharmacists in hospital settings have not yet been positioned to improve the prescribing and transcribing components of the medication-use process.

https://doi.org/10.1177/0018578719844707

[Article Title: Formulation and Stability Study of Omeprazole Oral Liquid Suspension for Pediatric Patients / Oriana Boscolo, Francesco Perra, Leandro Salvo, Fabián Buontempo, and Silvia Lucangioli, p. 314-322]

Abstract:

Objectives: To develop and to study the physicochemical and microbiological stability of omeprazole liquid oral formulations used as therapeutic agent in many acid-related disorders, for pediatric use. Furthermore, to optimize and validate a stability-indicating high-performance liquid chromatography (HPLC) method for the analysis of omeprazole in the studied formulations.

Method: Oral liquid suspensions of omeprazole were prepared at 2 mg/mL using crushed omeprazole pellets (formulation A) and pure omeprazole (formulation B) with a complete vehicle including humectant, suspending, sweetening, antioxidant, and flavoring agents. Samples were stored at 4°C and 25°C. Omeprazole content of each formulation was analyzed in triplicate using micro-HPLC at 0, 3, 7, 14, 30, 60, 90, 120, and 150 days. Other parameters were also determined, such as appearance, pH, resuspendibility, and viscosity. Microbiological studies were conducted according to the United Stated Pharmacopeia (USP) guidelines for non-sterile products.

Results: Formulation A stayed physicochemical and microbiologically stable at refrigerated (4°C) conditions during at least 150 days and it only stayed stable during 14 days at 25°C. Formulation B was stayed physicochemical and microbiologically stable at refrigerated (4°C) conditions at least 90 days, but it is not recommended to store at 25°C for more than 1 day.

Conclusions: Formulation A and formulation B can be stored for at least 150 and 90 days, respectively, at refrigerated conditions. Formulation A can be stored at room temperature for 14 days. Both formulations are perfectly suitable for pediatric patients who are usually notable to swallow solid oral formulations. The proposed analytical method was suitable for the study of stability of different formulations.

https://doi.org/10.1177/0018578719844704

[Article Title: Comparison of 3 Surveillance Methods to Detect Potential Controlled Substance Diversion in an Academic Medical Center / Catherine G. Derington, Ben R. Lopez, Robert J. Weber, and Crystal R. Tubbs, p. 323-331]

Abstract:

Objectives: To compare 3 methods of detecting potential diversion of controlled substances (CS) by health care personnel from inpatient units in a large, academic medical center.

Methods: Three different reports were retrospectively analyzed and evaluated to determine which employees are “high-risk” for diversion over a 30-day period using defined criteria. Reports were derived from automated dispensing machines (ADMs), purchased third-party software (TPS), and the electronic health record (EHR). The primary outcome was the percentage of employees in each report who were deemed to be high-risk for CS diversion (positive predictive value [PPV]). Secondary outcomes included the number of false positives and description of high-risk users on each report. Descriptive statistics were used to analyze differences between methods.

Results: The PPV was highly variable between reports. The PPVs among the ADM, TPS, and EHR reports were 3.28%, 6.82%, and 23.88%, respectively. False positives were high among all reports (96.72%, 93.18%, and 76.12% for the ADM, TPS, and EHR reports, respectively).

Conclusions: A report from the EHR has the highest PPV to detect high-risk employees who may be diverting CS. However, false positives were high for all reports, indicating that significant improvements are needed in the development of accurate and reliable software to detect potential and actual CS diversion.

https://doi.org/10.1177/0018578719844170

[Article Title: Compatibility of Y-Site Injection of Meropenem Trihydrate With 101 Other Injectable Drugs / Jean-Justin Lessard, Elaine Caron, Hugo Schérer, Jean-Marc Forest and Grégoire Leclair, p. 332-337]

Abstract:

Objective: The objective of the study was to establish the compatibility of injectable meropenem with 101 other drugs during Y-site administration.

Methods: Meropenem (50 mg/mL, 10 mL) was combined with 101 undiluted injectable drugs (10 mL each) at room temperature. Each preparation was performed twice. The first sample underwent a visual evaluation and a particle count test by light obstruction immediately after mixing. These tests were repeated 4 hours after mixing using the second preparation. Incompatibility was defined as precipitation or other visual change (turbidity, crystal formation, gas formation, color change) or failure to meet United States Pharmacopeia (USP) <788> 1.B specifications at any time point.

Results: A total of 83 of the 101 injectable drugs tested with meropenem were found to be compatible both visually and using the USP <788> particle counter. The gross incompatibility of the other 17 drugs was determined by visual observation. One mixture complied with the specifications, but showed an increase of temperature upon mixing and was removed from the study.

Conclusion: Of the 101 drugs tested, 83 were found to be compatible while the remaining 17 were incompatible. One drug was removed from the study as its compatibility was unclear.

https://doi.org/10.1177/0018578719844168

[Article Title: A Case of Antibiotic-Induced Posterior Reversible Encephalopathy Syndrome / Brian Wesley Gilbert, Ali Gabriel, and Laura Velazquez, p. 338-341]

Abstract:

Purpose: To report a case of posterior reversible encephalopathy syndrome (PRES) in a 75 year-old patient who was taking concomitant ciprofloxacin and metronidazole.

Method: Case report

Results: A patient had been prescribed ciprofloxacin and metronidazole during a recent hospitalization and continued this regimen outpatient. Two weeks after discharge and 3 weeks after initiation of her regimen, she was brought to the emergency department after developing acute weakness and lightheadedness. After admission, the patient declined more rapidly and began seizing with subsequent intubation. Initial computed tomographic (CT) imaging showed no acute neurological abnormalities, and a sepsis workup was initiated. After negative CT, a magnetic resonance imaging scan was performed that showed a T2 flair and hyperdensity consistent with PRES. The final diagnosis was considered to be PRES secondary to ciprofloxacin/metronidazole utilization.

Conclusion: Antibiotic induced PRES is a condition that needs to be explored more thoroughly.

https://doi.org/10.1177/0018578719844706